186,439 research outputs found
The role of the lectin VIP36 in the early secretory pathway
No full textLectins are of emerging importance for quality control and intracellular transport of glycoproteins in mammalian cells. One of the most prominent lectins involved in intracellular transport is ERGIC-53, which belongs to the family of L-type lectins. ERGIC-53 mediates the ER export of several glycoproteins like cathepsin Z, α1-antitrypsin (α1-AT) or blood coagulation factors. VIP36 belongs to the same family as ERGIC-53, but its cellular function remains poorly understood. VIP36 is a type I membrane protein. It cycles within the early secretory pathway and binds high mannose glycans. In order to gain insight into the function of VIP36 we decided to search for a luminal interaction partner for VIP36.
We used a YFP-protein fragmentation complementation (YFP-PCA) based FACS screen of a human adult liver library to unravel an interaction partner for VIP36. Complementation of YFP is irreversible. Therefore, the YFP-PCA is well suited to detect weak interactions, like those between mammalian lectins and glycoproteins. YFP2-VIP36 was used as the bait in our screen. The human liver library was tagged with YFP1. Our screen identified α1-AT as an interaction partner for VIP36. VIP36 recognized high mannose containing α1-AT, which is consistent with the previously obtained results about the glycan affinity of VIP36. This interaction was increased upon inhibition of complex glycosylation by kifunensine. The complex formed by α1-AT and VIP36 was localized to the Golgi and the ER. α1-AT was previously identified as a cargo for ERGIC-53. Knockdown of ERGIC-53 slowed down α1-AT transport, consistent with a role for ERGIC-53 in ER export of α1-AT. In contrast, knockdown of VIP36 accelerated transport of endogenous α1-AT in HepG2 cells. This effect was specific for α1-AT, as the non-glycosylated protein albumin showed no acceleration in transport. In addition, VIP36 knockdown did not affect general protein secretion. This finding makes it unlikely that VIP36 acts as an anterograde cargo receptor for α1-AT. Further studies on the dynamics of the complex formed by VIP36 and α1-AT revealed that VIP36 recycles α1-AT back to the ER, which argues for a role of VIP36 in post-ER quality control. This notion is further supported by the finding that the chaperone BiP co-immunoprecipitated with the complex of VIP36 and α1-AT. This chaperone was previously described as an interaction partner for VIP36. This argues for a complex consisting of VIP36 and BiP acting together in post-ER quality control to detect misfolded α1-antitrypsin in the Golgi and retrieve it back to the ER.
Apart from searching for an interaction partner, I also determined the effect of depletion of VIP36 on the morphology of the secretory pathway. The rationale behind this is the observation that cargo receptors contribute to the structural integrity of organelles of the secretory pathway. Knockdown of VIP36 had no effect on ER exit sites or on the ERGIC. However, VIP36 knockdown resulted in fragmentation of the Golgi apparatus. The fragmented Golgi was not the consequence of disturbed bidirectional protein transport and not due to effects on microtubules. Knockdown of VIP36 reduced COPI staining on the Golgi. VIP36 is likely to provide COPI binding sites on the Golgi via its cytosolic tail and thereby contribute to Golgi structural integrity. Our results underscore the importance of cargo receptors, not only for intracellular transport within the secretory pathway, but also to maintain the integrity of the secretory pathway itself.
In conclusion, my thesis provides a deeper insight into the function of VIP36 in the early secretory pathway
Friedrich Vinzenz Reiterer, Gerechtigkeit als Heil. צדק bei Deuterojesaja. Aussage und Vergleich mit der alttestamentliche Tradition. 1976
No full textBogaert Pierre-Maurice. Friedrich Vinzenz Reiterer, Gerechtigkeit als Heil. צדק bei Deuterojesaja. Aussage und Vergleich mit der alttestamentliche Tradition. 1976. In: Revue théologique de Louvain, 9ᵉ année, fasc. 2, 1978. p. 214
Friedrich V. Reiterer, « Alle Weisheit stammt vom Herrn… » Gesammelte Studien zu Ben Sira., Berlin – New York, W. de Gruyter, 2007
No full textJoosten Jan. Friedrich V. Reiterer, « Alle Weisheit stammt vom Herrn… » Gesammelte Studien zu Ben Sira., Berlin – New York, W. de Gruyter, 2007. In: Revue d'histoire et de philosophie religieuses, 88e année n°2, Avril-Juin 2008. p. 249
Friedrich Vinzenz Reiterer, Gerechtigkeit als Heil. צדק bei Deuterojesaja. Aussage und Vergleich mit der alttestamentliche Tradition. 1976
No full textBogaert Pierre-Maurice. Friedrich Vinzenz Reiterer, Gerechtigkeit als Heil. צדק bei Deuterojesaja. Aussage und Vergleich mit der alttestamentliche Tradition. 1976. In: Revue théologique de Louvain, 9ᵉ année, fasc. 2, 1978. p. 214
Friedrich V. Reiterer, « Alle Weisheit stammt vom Herrn… » Gesammelte Studien zu Ben Sira., Berlin – New York, W. de Gruyter, 2007
No full textJoosten Jan. Friedrich V. Reiterer, « Alle Weisheit stammt vom Herrn… » Gesammelte Studien zu Ben Sira., Berlin – New York, W. de Gruyter, 2007. In: Revue d'histoire et de philosophie religieuses, 88e année n°2, Avril-Juin 2008. p. 249
Global-local characterization and numerical modeling of TWB laser welded joints
No full textSheet forming of tailor welded blanks (TWBs) of advanced high strength steels is complex because of the notable differences in mechanical properties, and hence in formability, of base metals, heat affected zones and weld seam. In this work, an accurate characterization of the mechanical behavior of these regions in TWBs made of a DP and TRIP steel was carried out. Micro-samples, machined from base metals and fusion zone were employed to retrieve the local constitutive laws up to fracture. At the same time, macro-samples, extracted throughout the welded joint were tested to assess the weldment overall behavior. Along with global load-displacement data, strain and displacement fields of the joint were evaluated, using a Digital Image Correlation technique. An FE simulation of the entire joint was setup, using the previously identified material properties. In a comparison between the FE model and experiments, good results were obtained both at a global and local level, up to fractur
Online k-step PNARX identification for nonlinear engine systems
No full textReal systems are often nonlinear, and accounting for the nonlinearity can be essential for the attainable closed-loop performance in model-based control. This is especially true for many engine related control problems, as the achievable tradeoff between different targets, e.g. emissions and consumption, depends strongly on the model quality. However, engine systems tend to change over time, and it would be beneficial to be able to track these changes in the model. Against this background, we propose here a novel recursive algorithm for online adaptive system identification aimed to estimate an approximating parametric nonlinear model (polynomial NARX) of systems. This model structure has been used earlier e.g. for the air path control. The presented identification scheme is also suitable for parameter estimation in a closed-loop setting, provided that the data is sufficiently exciting. The main contribution of this paper is a recursive algorithm minimizing the k-step ahead prediction error for updating the model parameters in a computationally efficient way. We show its effectiveness by means of simulation examples of a nonlinear case study system and real data of a Diesel engine air path
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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